Pertussis (Whooping Cough) is prevented by vaccination and treated with antibiotics such as azithromycin or erythromycin.
MOTIVATION AND BACKGROUND:
Pertussis, or whooping cough, is an infectious respiratory disease caused by the bacterium Bordetella pertussis attaching to the ciliated cells in the upper respiratory track and releasing toxins that destroy the cilia, causing inflammation. Patients experience frequent, violent coughing fits and often make high-pitched whooping sounds as they gasp for air after one of these episodes, hence the name whooping cough. After an incubation period of one to two weeks, the patient begins to experience symptoms and the disease can be divided into three stages. The first stage is the catarrhal phase during which the patient is highly contagious, experiences a low-grade fever, and develops a milder cough. The second stage is the paroxysmal phase during which the patient experiences severe, violent coughing fits generally for two to four weeks (although in some cases this stage can last for more than ten weeks). The patient’s cough then gradually subsides over an additional one to three weeks during the convalescent stage [3]. Typically complications with pertussis arise during the paroxysmal stage. Teens and adults report loss of bladder control, passing out, and even rib fractures caused by the severity of the coughing fits themselves, but pertussis is very rarely fatal in an older age group. Complications are much more severe in infants and small children, and more than half of children infected by pertussis before they reach one year of age require hospitalization. Children are more susceptible to death as a consequence of pertussis, especially in areas of the world where vaccinations are not readily available [1]. Since the invention of the pertussis vaccine in the 1940s, children in the United States are routinely vaccinated and the number of infections per year has plummeted. But recently the number of pertussis infections has been climbing, and in 2012 the United States experienced the most reported cases of pertussis since 1955 [1]. Worldwide, there are twenty to forty million reported cases and between 200 and 400 thousand child deaths caused by pertussis each year [2]. This increase in pertussis cases is due partly to increased awareness and better diagnostic testing, meaning that more cases are reported simply because the disease is more likely to be identified. But, the pertussis vaccination may also be becoming less effective as immunity to the infection wanes [1].
TARGET INFORMATION:
Whooping cough is caused by the bacterium Bordetella pertussis, an aerobic, gram-negative, coccobacillus [2] roughly 0.8 μm by 0.4 μm in size [3]. The bacteria thrive in the mucus of the human respiratory tract multiply exponentially after colonization, but only on ciliated cells [3]. The disease is usually passed from person to person via mucus droplets infected with Bordetella pertussis expelled from an infected person whilst coughing [4]. The bacteria are capable of living outside the body for a few days, so it is possible for the disease to be spread by contaminated objects, although this is more unlikely [3].Once a Bordetella pertussis bacterium makes it inside the human body, it produces several different virulence factors to defeat the host’s immune system and induce infection. The first stepis for the bacterium to attach to the ciliated cells in the respiratory tract by producing adhesive proteins. Once the bacteria attach, they must defeat the host’s immune system to achieve infection. The bacterium produces a toxin, called Pertussis Toxin, which allows infection to take place [4]. Pertussis Toxin (shown below in Figure 1) is composed of five subunits, each of which contain roughly 100 residues [5]. Some of the subunits are responsible for binding to the cell, allowing the other active subunits to enter the cell, interfere with receptor pathways, and inhibit cellular communication that signals neutrophils, lymphocytes, and macrophages to reach the area of infection. Without this communication, the bacteria are free to colonize without interference from the host’s immune response. After colonization, the bacteria produce many more toxins that damage and kill the host’s epithelial cells. The toxin that causes the most damage is tracheal cytotoxin, and the characteristic whooping cough associated with pertussis is a result of its damage to the tracheal cells [4].
Figure 1: Schematic of the Pertussis Toxin (PT Toxin)
DRUG INFORMATION:
The best way to treat pertussis is preventatively – if the patient is vaccinated adequately before being exposed to the disease then they are unlikely to contract the it, and even if they do, it is much less severe. Today, the pertussis vaccine includes an acellular version of Bordetella pertussis with several different of the toxins it produces. The vaccine is combined with the tetanus and diphtheria vaccines as either DTaP or Tdap. DTaP is for children younger than seven years of age, and Tdap is for older children, teens, and adults. Before the age of seven, children should receive five doses of the DTaP vaccine, and then a single dose of the Tdap vaccine between eleven and eighteen years of age. Adults need only a single dosage of the Tdap vaccine, but pregnant women should receive a dose of the Tdap vaccine during every pregnancy, preferably during the third trimester so that antibodies can be passed through the mother to the unborn child [1]. ]If infection occurs, pertussis is treated with oral antibiotics. Treatment is most effective if administered within first seven days of infection. Antibiotics will not shorten the duration of the disease but will help eradicate the bacteria from the body so the patient is no longer contagious. Antibiotics do not treat the symptoms of pertussis – they simply kill the source [4].There is debate as to which antibiotic is the best for treating pertussis. Typically either erythromycin (CAS number 114-07-8) or azithromycin (CAS number 83905-01-5) is prescribed.Erythromycin is typically the drug of choice to treat pertussis except in very young and patients taking several other medications [4]. Despite its effectiveness in treating pertussis, erythromycin has been know to cause severe gastrointestinal discomfort, so some physicians may choose not to prescribe it because of that [4]. The chemical formula for Erythromycin is C37H67NO13 and its molecular weight is 733.93 grams. A schematic of the drug is shown below in Figure 2. Erythromycin works by disrupting the function of the bacterium’s ribosomes, thus inhibiting protein synthesis and causing the bacterium to die [6].
Figure 2: Schematic of Erythromycin
Patients under a month of age are typically prescribed azithromycin instead of erythromycin, because erythromycin has been associated with hypertrophic pyloric stenosis in infants [4]. Azithromycin is a derivative of erythromycin and works in essentially the same way [6]. Additionally. azithromycin is typically prescribed to patients taking several other medications because it has fewer potential drug interactions than erythromycin [4]. The chemical formula for azithromycin is C38H72N2O12 and it has a molecular weight of 748.98 grams. A schematic of the drug is show below in Figure 3.
Figure 3: Schematic of Azithromycin
More information about Pertussis can be found at the Center for Disease Control and Prevention webpage.
Galiza, E.; Heath, P., Pertussis. Medicine 2009, 37(12), 635-637.
Finger, H.; Wirsing von Koenig, C. H. Medical Microbiology; The University of Texas Medical Branch at Galveston, 1996.
Spector, T.; Maziarz, E., Pertussis. Medical Clinics of North America 2013, 97(4).
Stein, P.; Boodhoo, A.; Armstrong, G. D.; Cockle, S. A.; Klein, M. H.; Read, R. J., The crystal structure of pertussis toxin. Structure 1994, 2(1), 45-57.
Ginsburg, C. M.; Eichenwald, H. F., Erythromycin: A review of its uses in pediatric practice. The Journal of Pediatrics, 1976, 89(6), 872-884.
DISEASE/DRUG OF INTEREST:
Pertussis (Whooping Cough) is prevented by vaccination and treated with antibiotics such as azithromycin or erythromycin.MOTIVATION AND BACKGROUND:
Pertussis, or whooping cough, is an infectious respiratory disease caused by the bacterium Bordetella pertussis attaching to the ciliated cells in the upper respiratory track and releasing toxins that destroy the cilia, causing inflammation. Patients experience frequent, violent coughing fits and often make high-pitched whooping sounds as they gasp for air after one of these episodes, hence the name whooping cough. After an incubation period of one to two weeks, the patient begins to experience symptoms and the disease can be divided into three stages. The first stage is the catarrhal phase during which the patient is highly contagious, experiences a low-grade fever, and develops a milder cough. The second stage is the paroxysmal phase during which the patient experiences severe, violent coughing fits generally for two to four weeks (although in some cases this stage can last for more than ten weeks). The patient’s cough then gradually subsides over an additional one to three weeks during the convalescent stage [3]. Typically complications with pertussis arise during the paroxysmal stage. Teens and adults report loss of bladder control, passing out, and even rib fractures caused by the severity of the coughing fits themselves, but pertussis is very rarely fatal in an older age group. Complications are much more severe in infants and small children, and more than half of children infected by pertussis before they reach one year of age require hospitalization. Children are more susceptible to death as a consequence of pertussis, especially in areas of the world where vaccinations are not readily available [1]. Since the invention of the pertussis vaccine in the 1940s, children in the United States are routinely vaccinated and the number of infections per year has plummeted. But recently the number of pertussis infections has been climbing, and in 2012 the United States experienced the most reported cases of pertussis since 1955 [1]. Worldwide, there are twenty to forty million reported cases and between 200 and 400 thousand child deaths caused by pertussis each year [2]. This increase in pertussis cases is due partly to increased awareness and better diagnostic testing, meaning that more cases are reported simply because the disease is more likely to be identified. But, the pertussis vaccination may also be becoming less effective as immunity to the infection wanes [1].TARGET INFORMATION:
Whooping cough is caused by the bacterium Bordetella pertussis, an aerobic, gram-negative, coccobacillus [2] roughly 0.8 μm by 0.4 μm in size [3]. The bacteria thrive in the mucus of the human respiratory tract multiply exponentially after colonization, but only on ciliated cells [3]. The disease is usually passed from person to person via mucus droplets infected with Bordetella pertussis expelled from an infected person whilst coughing [4]. The bacteria are capable of living outside the body for a few days, so it is possible for the disease to be spread by contaminated objects, although this is more unlikely [3].Once a Bordetella pertussis bacterium makes it inside the human body, it produces several different virulence factors to defeat the host’s immune system and induce infection. The first stepis for the bacterium to attach to the ciliated cells in the respiratory tract by producing adhesive proteins. Once the bacteria attach, they must defeat the host’s immune system to achieve infection. The bacterium produces a toxin, called Pertussis Toxin, which allows infection to take place [4]. Pertussis Toxin (shown below in Figure 1) is composed of five subunits, each of which contain roughly 100 residues [5]. Some of the subunits are responsible for binding to the cell, allowing the other active subunits to enter the cell, interfere with receptor pathways, and inhibit cellular communication that signals neutrophils, lymphocytes, and macrophages to reach the area of infection. Without this communication, the bacteria are free to colonize without interference from the host’s immune response. After colonization, the bacteria produce many more toxins that damage and kill the host’s epithelial cells. The toxin that causes the most damage is tracheal cytotoxin, and the characteristic whooping cough associated with pertussis is a result of its damage to the tracheal cells [4].DRUG INFORMATION:
The best way to treat pertussis is preventatively – if the patient is vaccinated adequately before being exposed to the disease then they are unlikely to contract the it, and even if they do, it is much less severe. Today, the pertussis vaccine includes an acellular version of Bordetella pertussis with several different of the toxins it produces. The vaccine is combined with the tetanus and diphtheria vaccines as either DTaP or Tdap. DTaP is for children younger than seven years of age, and Tdap is for older children, teens, and adults. Before the age of seven, children should receive five doses of the DTaP vaccine, and then a single dose of the Tdap vaccine between eleven and eighteen years of age. Adults need only a single dosage of the Tdap vaccine, but pregnant women should receive a dose of the Tdap vaccine during every pregnancy, preferably during the third trimester so that antibodies can be passed through the mother to the unborn child [1]. ]If infection occurs, pertussis is treated with oral antibiotics. Treatment is most effective if administered within first seven days of infection. Antibiotics will not shorten the duration of the disease but will help eradicate the bacteria from the body so the patient is no longer contagious. Antibiotics do not treat the symptoms of pertussis – they simply kill the source [4].There is debate as to which antibiotic is the best for treating pertussis. Typically either erythromycin (CAS number 114-07-8) or azithromycin (CAS number 83905-01-5) is prescribed.Erythromycin is typically the drug of choice to treat pertussis except in very young and patients taking several other medications [4]. Despite its effectiveness in treating pertussis, erythromycin has been know to cause severe gastrointestinal discomfort, so some physicians may choose not to prescribe it because of that [4]. The chemical formula for Erythromycin is C37H67NO13 and its molecular weight is 733.93 grams. A schematic of the drug is shown below in Figure 2. Erythromycin works by disrupting the function of the bacterium’s ribosomes, thus inhibiting protein synthesis and causing the bacterium to die [6].More information about Pertussis can be found at the Center for Disease Control and Prevention webpage.
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